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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November - December 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Titanium carbide
- Substance type: inorganic
- Physical state: grey solid
- Analytical purity: ≥ 99%
- Lot/batch No.: 82496
- Expiration date of the lot/batch: not applicable
- Storage condition of test material: room temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approximately 13 weeks old
- Weight at study initiation: > 2 kg
- Housing: ABS - plastic rabbit cages, floor 4200 cm²
- Diet: Free access to autoclaved hay and to Altromin 2123 maintenance diet for rabbits (lot no. 1516), rich in crude fibre
- Water: Free access to tap water (drinking water, municipal residue control, microbiological controls at regular intervals)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Acclimation period: at least 5 days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C (recommendations of TVT, GV-SOLAS)
- Humidity (%): 55 ± 10 °C
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 h : 12 h

TVT = TVT Tierärztliche Vereinigung für Tierschutz, Merkblatt 127 zur Tiergerechten Haltung von Versuchskaninchen, 2010
GV-SOLAS = Planung, Struktur von Versuchstierbereichen tierexperimentell tätiger Institutionen; Veröffentlichung GV-SOLAS (Gesellschaft für Versuchstierkunde, Society for Laboratory Animal Science), Mai 1988

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of each animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
72 h (the treated eye was not rinsed 24 hours after the application.)
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: none

SCORING SYSTEM: see "Any other information on materials and methods incl. table"

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Basis:
other: animals #1, #2, and #3
Time point:
other: 1, 24, 48, 72 h (mean values)
Score:
>= 0.33 - <= 0.67
Max. score:
1
Reversibility:
fully reversible
Remarks on result:
other: For details see "Any other information on results incl. tables"
Irritation parameter:
chemosis score
Basis:
other: animals #1, #2, and #3
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
other: animals #1, #2, and #3
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Basis:
other: animals #1, #2, and #3
Time point:
other: 1, 24, 48, 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
- First time of effects, all animals: 1 hour post-application redness grade 1
- Last time of effects:
* animal no. 1: 48 hours post-application redness grade 1
* animal no. 2 and no. 3: 24 hours post-application redness grade 1
- Reversibility of the observed effects:
* animal no. 1: the changes were fully reversible within 72 hours post-application
* animal no. 2 and no. 3: the changes were fully reversible within 48 hours post-application

Any other information on results incl. tables

Table 2: Mean Values of Eye Irritation Scores – (24, 48, 72 Hour Reading)

Animal No. 

Sex

Conjunctival

Redness

Conjunctival

Chemosis

Iris Cornea

Opacity

1

female

0.67

0.00 

0.00 

0.00 

2

female

0.33

0.00 

0.00 

0.00 

3

female

0.33

0.00 

0.00 

0.00 

 

Evaluation of Results

Individual reactions of each animal were recorded at each time of observation. Nature, severity and duration of all lesions observed were described. For the calculation only the 24, 48 and 72-hour readings were used.

On the basis of the test results, the test substance was classified in any of the following classes in conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC:

R36 Irritating to eyes:

Substances and preparations which, when applied to the eye of the animal, cause significant ocular lesions which occur within 72 hours after exposure and which persists for at least 24 hours.

Ocular lesions are significant if the mean scores of the eye irritation test cited in Annex B.5 to Commission Regulation (EC) No. 440/2008, L 142 have any of the following values:

- corneal opacity ≥ 2 but < 3

- iris lesion ≥ 1 but ≤ 1.5,

- redness of the conjunctiva ≥ 2.5,

- oedema of the conjunctiva (chemosis) ≥ 2,

or, in case where Annex B.5 test have been completed using three animals if the lesions, on two or more animals, are equivalent to any of the above values except that for iris lesion the value should be ≥ 1 but < 2 and for redness of the conjunctiva the value should be ≥ 2.5. In both cases all scores at each of the reading times (24, 48 and 72 hours) for an effect should be used in calculating the respective mean values.

- Substances or preparations which cause significant ocular lesions, based on practical experience in humans.

- Organic peroxides except where evidence to the contrary is available.

R41 Risk of serious damage to eyes

Substances and preparations which, when applied to the eye of the animal cause severe ocular lesions which occur within 72 hours after exposure and which persist for at least 24 hours. O

cular lesions are severe if the means of the scores of the eye irritation test cited in Annex B.5 to Commission Regulation (EC) No. 440/2008, L 142 have any of the values:

- cornea opacity ≥ 3,

- iris lesion > 1.5.

The same shall be the case where the test has been completed using three animals if these lesions, on two or more animals, have any of the values:

- cornea opacity ≥ 3,

- iris lesion = 2.

In both cases all scores at each of the reading times (24, 48 and 72 hours) for an effect should be used in calculating the respective mean values.

Ocular lesions are also severe when they are still present at the end of the time of observation.

Ocular lesions are also severe if the substance or preparation causes irreversible colouration of the eyes.

- Substances and preparations which cause severe ocular lesions, based on practical experience in humans.

Note:

When a substance or preparation is classified as corrosive and assigned R34 or R35, the risk of severe damage to eyes is considered implicit and R41 is not included in the label.

On the basis of the test results, the following risk phrases shall be assigned in conformity with the criteria given in Annex I of Regulation (EC) 1272/2008:

Eye irritant Category 1:

Irreversible effects on the eyes / serious damage to the eyes An eye irritant category 1 is a test material that produces:

- at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or that have not fully reversed within 21 days; and/or

- at least in 2 of 3 animals, a positive response of

(i) corneal opacity 3; and/or

(ii) iritis > 1.5

calculated as the mean scores following the grading at 24, 48 and 72 hours after instillation of the test material.

Eye irritant Category 2:

Reversible effects on the eyes/Irritating to the eyes

An eye irritant category 2 is a test material that produces:

- at least in 2 of 3 animals, a positive response of

(i) corneal opacity 1; and/or

(ii) iritis 1; and/or

(iii) conjunctival redness 2; and/or

(iv) conjunctival oedema (chemosis) 2

calculated as the mean scores following the grading at 24, 48 and 72 hours after instillation of the test material, and which fully reverse within an observation period of 21 days.

On the basis of the test results, the following risk phrases may be assigned in conformity with the criteria given in GHS - Globally Harmonized System of Classification and Labelling of Chemicals, third revised edition, July 2009:

Category 1: An eye irritant Category 1 (irreversible effects on the eye) is a test material that produces:

- at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or that have not fully reversed within 21 days; and/or

- at least in 2 of 3 animals, a positive response of

(i) corneal opacity 3; and/or

(ii) iritis > 1.5

calculated as the mean scores following the grading at 24, 48 and 72 hours after instillation of the test material.

Category 2A: An eye irritant Category 2A (irritating to eyes) is a test material that produces:

- at least in 2 of 3 animals, a positive response of

(i) corneal opacity 1; and/or

(ii) iritis 1; and/or

(iii) conjunctival redness 2; and/or

(iv) conjunctival oedema (chemosis) 2

calculated as the mean scores following the grading at 24, 48 and 72 hours after instillation of the test material, and which fully reverse within 21 days.

Category 2B: Within this category an eye irritant is considered mildly irritating to eyes (Category 2B), when the effects listed above are fully reversible within 7 days of observation.

Results:

After the application into the eyes of three female NZW rabbits the test item produced irritant but no corrosive effects (see Tables 3 to 5).

Neither mortalities nor significant clinical signs of toxicity were observed (Table 6).

The eyes were not rinsed after the application.

Upon fluorescein examinations at the end of the observation period of 72 hours no corneal lesions were found in any animal.

Conjunctival redness was observed in all animals and are individually described in Tables 3 to 6.

Table 3: Eye Irritation Scores – Animal No. 1

Single Data

 

Time Post-Application

Average

Score

(24, 48 and

72 hours)

1 hour

24 hours

48 hours

72 hours

T/C

T/C

T/C

T/C

Conjunctival

Redness

1/0

1/0

1/0

0/0

0.67

Conjunctival

Chemosis

0/0

0/0

0/0

0/0

0

Iris

0/0

0/0

0/0

0/0

0

Cornea

0/0

0/0

0/0

0/0

0

T = Test item, C = control

Table 4: Eye Irritation Scores – Animal No. 2 

Single Data

 

Time Post-Application

Average

Score

(24, 48 and

72 hours)

1 hour

24 hours

48 hours

72 hours

T/C

T/C

T/C

T/C

Conjunctival

Redness

1/0

1/0

0/0

0/0

0.33

Conjunctival

Chemosis

0/0

0/0

0/0

0/0

0

Iris

0/0

0/0

0/0

0/0

0

Cornea

0/0

0/0

0/0

0/0

0

T = test item, C = control

Table 5: Eye Irritation Scores – Animal No. 3

Single Data

 

Time Post-Application

Average

Score

(24, 48 and

72 hours)

1 hour

24 hours

48 hours

72 hours

T/C

T/C

T/C

T/C

Conjunctival

Redness

1/0

1/0

0/0

0/0

0.33

Conjunctival

Chemosis

0/0

0/0

0/0

0/0

0

Iris

0/0

0/0

0/0

0/0

0

Cornea

0/0

0/0

0/0

0/0

0

T = test item, C = control

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In this study, titanium carbide is not irritant to the eye.
Executive summary:

In a primary eye irritation study according to OECD 405, 0.1 g of titanium carbide was instilled into the conjunctival sac of one eye each of three female New Zealand White rabbits (age approximately 13 weeks). Eyes were not washed. Animals were observed for a total of 72 hours. Irritation was scored by evaluating conjunctival redness, conjunctival chemosis, iris, and cornea

Only slight effects have been observed which were fully reversible within 72 hours. Neither mortalities nor significant clinical signs of toxicity were observed. In this study, titanium carbide is not an eye irritant.